聚乙二醇化赛妥珠单抗治疗斑块状银屑病的长期疗效：两项随机III期试验（CIMPASI-1和CIMPASI-2）的3年结果

Long-term efficacy of certolizumab pegol for the treatment of plaque psoriasis: 3-year results from two randomized phase III trials (CIMPASI-1 and CIMPASI-2).

作者信息

Gordon K B, Warren R B, Gottlieb A B, Blauvelt A, Thaçi D, Leonardi C, Poulin Y, Boehnlein M, Brock F, Ecoffet C, Reich K

机构信息

Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI, USA.

Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, The University of Manchester, Manchester, UK.

出版信息

Br J Dermatol. 2021 Apr;184(4):652-662. doi: 10.1111/bjd.19393. Epub 2020 Sep 9.

BACKGROUND

Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-tumour necrosis factor biologic.

OBJECTIVES

To report the 3-year efficacy of CZP in plaque psoriasis, pooled from the CIMPASI-1 (NCT02326298) and CIMPASI-2 (NCT02326272) phase III trials.

METHODS

Adults with moderate-to-severe psoriasis for ≥ 6 months were randomized 2 : 2 : 1 to CZP 200 mg, CZP 400 mg or placebo, every 2 weeks (Q2W) for up to 48 weeks. Patients entering the open-label period (weeks 48-144) from double-blinded CZP initially received CZP 200 mg Q2W. Patients not achieving ≥ 50% improvement in Psoriasis Area and Severity Index (PASI 50) at week 16 entered an open-label CZP 400 mg Q2W escape arm (weeks 16-144). Dose adjustments based on PASI response were permitted during open-label treatment. Outcomes included PASI 75, PASI 90 and Physician's Global Assessment (PGA) 0/1 responder rates, based on a logistic regression model (missing data imputed using Markov Chain Monte Carlo methodology).

RESULTS

In total, 186 patients were randomized to CZP 200 mg Q2W and 175 to CZP 400 mg Q2W. At week 48, PASI 75/90 was achieved by 72·7%/51·3% of patients randomized to CZP 200 mg and 84·4%/62·7% randomized to CZP 400 mg. Patients entering the open-label period at week 48, from blinded treatment, received CZP 200 mg Q2W. At week 144, PASI 75/90 was achieved by 70·6%/48·7% patients randomized to CZP 200 mg and 72·9%/42·7% randomized to CZP 400 mg. At week 16, 72 placebo-randomized patients entered the CZP 400 mg Q2W escape arm; 75.7%/58.5% achieved PASI 75/90 at week 144.

CONCLUSIONS

Both CZP 200 mg and 400 mg Q2W demonstrated sustained, durable efficacy, with numerically higher responses for some outcomes with 400 mg Q2W.

背景

赛妥珠单抗（CZP）是一种无Fc段、聚乙二醇化的抗肿瘤坏死因子生物制剂。

目的

报告从CIMPASI-1（NCT02326298）和CIMPASI-2（NCT02326272）III期试验汇总得出的CZP治疗斑块状银屑病的3年疗效。

方法

中度至重度银屑病病程≥6个月的成人患者按2∶2∶1随机分组，分别接受每2周一次（Q2W）的200 mg CZP、400 mg CZP或安慰剂治疗，最长治疗48周。从双盲期进入开放标签期（第48 - 144周）的最初接受200 mg Q2W CZP治疗的患者，在第16周时银屑病面积和严重程度指数（PASI）改善未达到≥50%（PASI 50）的患者进入开放标签的400 mg Q2W CZP挽救治疗组（第16 - 144周）。在开放标签治疗期间允许根据PASI反应进行剂量调整。基于逻辑回归模型（使用马尔可夫链蒙特卡罗方法估算缺失数据）得出的结果包括PASI 75、PASI 90以及医师整体评估（PGA）0/1反应率。

结果

总共186例患者被随机分配至每2周一次的200 mg CZP组，175例被随机分配至每2周一次的400 mg CZP组。在第48周时，随机分配至200 mg CZP组的患者中72.7%/51.3%达到PASI 75/90，随机分配至400 mg CZP组的患者中84.4%/62.7%达到PASI 75/90。在第48周从盲法治疗进入开放标签期的患者接受每2周一次的200 mg CZP治疗。在第144周时，随机分配至200 mg CZP组的患者中70.6%/48.7%达到PASI 75/90，随机分配至400 mg CZP组的患者中72.9%/42.7%达到PASI 75/90。在第16周时，72例接受安慰剂治疗的随机分组患者进入每2周一次的400 mg CZP挽救治疗组；在第144周时75.7%/58.5%的患者达到PASI 75/90。